Nucleic acid-binding polymers as anti-inflammatory agents
Nucleic acid-binding polymers as anti-inflammatory agents
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DOI：
10.1073/pnas.1105777108
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发表时间：
2011-08-23
影响因子：
11.1
通讯作者：
Sullenger, Bruce A.
中科院分区：
文献类型：
--
作者：
Lee, Jaewoo;Sohn, Jang Wook;Sullenger, Bruce A.
死亡和垂死的细胞释放核酸。这些细胞外 RNA 和 DNA 可以被炎症细胞摄取并激活多种核酸感应 Toll 样受体（TLR3、7、8 和 9）。这些 TLR 的不当激活会引发多种炎症和自身免疫性疾病。 TLR家族的冗余性鼓励我们寻找能够中和任何核酸促炎作用的材料，无论其序列、结构或化学性质如何。在此，我们证明某些核酸结合聚合物可以抑制所有核酸感应TLR的激活，无论它们是否识别ssRNA、dsRNA或低甲基化DNA。此外，全身施用此类聚合物可以预防小鼠急性中毒性休克模型中促炎性核酸引起的致命性肝损伤。因此，这些聚合物代表了一类新型抗炎剂，可以作为分子清除剂来中和各种核酸的促炎作用。
Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundancy of the TLR family encouraged us to seek materials that can neutralize the proinflammatory effects of any nucleic acid regardless of its sequence, structure or chemistry. Herein we demonstrate that certain nucleic acid-binding polymers can inhibit activation of all nucleic acid-sensing TLRs irrespective of whether they recognize ssRNA, dsRNA or hypomethylated DNA. Furthermore, systemic administration of such polymers can prevent fatal liver injury engendered by proinflammatory nucleic acids in an acute toxic shock model in mice. Therefore these polymers represent a novel class of anti-inflammatory agent that can act as molecular scavengers to neutralize the proinflammatory effects of various nucleic acids.